Hello, first post here, from the husband of a dear wife recently diagnosed with a Grade IV glioblastoma. Red flags at a UCLA Urgent Care led to a ct scan followed by an MRI and admission. Complete resection was performed 30 hours later. She followed up with radiochem, and is now in her second course of adjuvant Temodar. We were approved for Optune and are now two weeks in with that, holding firm at about 95% compliance and are also madly ingesting basically everything in the "A" list from the list in the library, thanks to a lot of wonderful help from Mike B here.
Anyway, our doctor suggested we might benefit from a drug called Tagrisso, from AstraZeneca Medicines. Don't see anything about that in the stacks so far, so was wondering if anyone has any thoughts regarding it. It's proven to be an efficacious treatment for lung cancer but could have crossover value since apparantly it crosses the BBB.
Welcome to our group. Sorry to hear of her diagnosis, but glad to hear a complete resection could be done.
ReplyDeleteWas the Tagrisso (osimertinib) recommended on the basis of genetic testing showing EGFR mutation/amplification?
Osimertinib works most potently in cells with specific EGFR mutations, so it's important to know if an EGFR mutation was found, and if so what was the specific mutation?
Mouse models show that osimertinib is active against tumors with the EGFRvIII ("variant 3") mutation.
https://academic.oup.com/neuro-oncology/article-abstract/19/suppl_6/vi82/4591000?redirectedFrom=fulltext
If her tumor is EGFR mutated/amplified, chloroquine (a malaria drug) could also be an important addition, as EGFR-driven tumors can be very dependent on autophagy and chloroquine can counteract this.
https://www.ncbi.nlm.nih.gov/pubmed/29377763
EGFRvIII expression triggers a metabolic dependency and therapeutic vulnerability sensitive to autophagy inhibition
Her genomic report stated: "EGFR A289T, amplification, EGFRvIII, T263P - subclonal" Her doctor came up with the Tagrisso after I lobbied to find something to deal with the EGFR problem. We discussed chloroquine and he said it was unusual for someone in Los Angeles to suffer from Malaria. We discussed the side effects of the chloroquine as well. It's on our 'to do' list, though. Did I provide the information you needed to form a conclusion as to the Tagrisso's efficacy? Thanks in advance for all you do.
DeleteThanks. The fact that EGFRvIII was positive gives sufficient rationale to try Tagrisso in my opinion, if only on the basis of mouse studies.
DeleteYes, I'm sure malaria is indeed rare in LA. If you're unable to obtain chloroquine, hydroxychloroquine would also be an option, though these are two different drugs and the retrospective clinical data linking chloroquine and EGFRvIII was done with chloroquine rather than hydroxychloroquine. I would probably still try hydroxychloroquine if chloroquine could not be obtained.
As we hoped, the insurance company denied the Rx for Tagrisso so it's off to the access process to see if we can get it. I'm fairly sure we can probably find a way to get the chloroquine, even in Los Angeles. I don't know if we're supposed to name names, but I will say that our team over at UCLA has been absolutely super so far.
DeleteI've met Dr. Cloughesy and I've heard very good reports about Dr. Linda Liau and Dr. Albert Lai. I think you're in good hands at UCLA. It's one of the few places I would want to be in your position.
DeleteThere is a clinical trial at St. Johns with a pulse-dosed EGFR inhibitor. The companies might offer these on compassionate use if you get a doctor to push for it.
DeleteWhich EGFR inhibitor? Many of them have already been tried in GBM (with no great results). Of course using different dosing regimens could make a difference.
DeleteThe 18th Annual Brain Tumor Conference was a couple of weeks ago there; it was very interesting, to say the least. It was great to see all of our doctors up there giving presentations and all of the sessions I observed were great. Dr. Liau was unable to attend so her place was taken by the neurosurgeon who performed our operation, Dr. Won Kim. What an ace !! Well, we are hoping 96% compliance with the Optune, the complete resection, the followup care and the 25 different supplements in the current cocktail do their job.
DeleteWe are trying to go to duke university and join one of their clinical trials involving injecting virus directly into the Glioblastoma. looks promising, Duke and Stamford in California have the widest available clinical trials for this disease
ReplyDeleteHello, you make also want to check out City of Hope’s Clinical Trial of CAR-T Therapy where they use an implanted catheter directly into tumor to inject the patients reengineered T cells. Involves memory and unleashes the immune system to target various GBM mutations
ReplyDeleteHello, You may....
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